Efficacy of a new delivery system based on solid lipid microparticles for the oral administration of the non-conventional antioxidant IAC on a diabetes mouse model

• Published in: Journal of endocrinological investigation 2018-10, Vol.41 (10), p.1227-1236
• Main Authors: Canistro, D., Vivarelli, F., Cirillo, S., Soleti, A., Albertini, B., Passerini, N., Merizzi, G., Paolini, M.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antioxidants; Antioxidants - administration & dosage; Blood Glucose - drug effects; Blood Glucose - metabolism; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - drug therapy; Drug delivery; Drug Delivery Systems - methods; Endocrinology; Glucose; Glucose tolerance; Humans; Hyperglycemia; Hypoglycemic Agents - administration & dosage; Insulin; Intolerance; Lipids; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Microparticles; Microspheres; Nicotinamide; Oral administration; Original Article; Particle Size; Random Allocation; Streptozocin; Treatment Outcome
• ISSN: 1720-8386; 0391-4097; 1720-8386
• DOI: 10.1007/s40618-018-0858-4

Purpose We previously showed the positive effects of the new antioxidant molecule bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) in reducing basal hyperglycaemia and relieving glucose intolerance in a diabetes model. However, the chemical properties of IAC did not allow an efficient oral administration, thus representing the main failing of that study. Here, we tested the effect of a new oral delivery system based on solid lipid microparticles (SLMs) in a diabetes mouse model. Methods The diabetes model was induced in C57B1/6J mice using streptozotocin and nicotinamide. Only the animals that overcame the glycaemic threshold of 180 mg/dL were enrolled in the study. Diabetic animals were then randomly assigned to 4 groups ( n  = 9) and treated once a day for 5 consecutive weeks with IAC (50, 100, and 150 mg/kg b.w.). The control group was composed of ( n  = 7) healthy mice that received only the vehicle. Glucose level was weekly monitored during the treatment period and up to 3 weeks after the suspension of the treatment. Glucose tolerance and insulin-resistance test were carried out. Results Our results showed that SLMs maintained the IAC effect in reducing basal hyperglycaemia as well as improving the insulin sensitivity and glucose tolerance. Conclusion The present study confirms that SLMs are promising drug carriers, which allow the oral administration of IAC ensuring its therapeutic efficacy. The concrete possibility to administer IAC per os represents a significant breakthrough in the putative consideration of this multi-radical scavenger in the diabetes therapeutic approach.